There are four general types of laxatives that are currently available: 1) bulk-forming; 2) osmotic; 3) stimulatory; 4) softening agents. The present application is directed toward the bulk-forming and osmotic types and specifically towards the use of an osmotic laxative in enhancing and correcting deficiencies found in bulk-forming laxatives.
While bulk-forming laxatives such as those formed from psyllium husks provide generally safe and effective laxatives, psyllium laxatives generally suffer from three primary deficiencies. First, bulk-forming laxatives such as psyllium are not directly compressible and lack the ability to be readily formulated in tabletted form. Second, they do not disperse well and often form lumps of psyllium material, the interiors of which are still substantially dry. Third, psyllium seed husk has very poor wetting qualities and therefore does not mix well.
The present invention addresses the poor compressibility of psyllium husk by combining the ground psyllium husk with a sugar alcohol, such as lactitol, which, as an osmotic laxative, has its own laxative properties.
Specifically, psyllium hydrophilic mucilloid has not yet successfully been provided in a tablet form but only in a powder form that may be dispersed in water. A chewable tablet containing psyllium would be beneficial because the masticating action in the mouth would aid dispersion. The present invention combines psyllium, which is not directly compressible, with a sugar alcohol to form a compressible granulate which may be compressed into tablets. Thus, the present invention provides a solution to problems inherent with one laxative--bulk-forming laxatives such as psyllium seed husks--by combining the bulk-forming laxative with another laxative--an osmotic laxative, such as lactitol.
By way of background, bulk-forming laxatives rely upon the use of dietary fiber. Dietary fiber is the portion of plant materials that is resistant to digestion. There are generally two types of dietary fiber: insoluble and soluble. Insoluble dietary fiber passes through the digestive system in a substantially intact form. Insoluble fiber passes through the digestive system quickly because it does not absorb water, like soluble fiber.
In contrast, soluble fiber absorbs water in the small intestine and in the stomach. Psyllium is one source of soluble fiber. Specifically, the psyllium form known as psyllium hydrophilic mucilloid consists of the husk (either milled or unmilled) of blond psyllium seeds. When exposed to water in the stomach and small intestine, the psyllium hydrophilic mucilloid forms a gelatinous mass which aids in the treatment of constipation by acting as a fecal softening agent and also acts to soothe and protect the small intestine.
However, obtaining an appropriate gelatinous mass of psyllium hydrophilic mucilloid in the small intestine is problematic due to the poor dispersability and mixability of the psyllium hydrophilic mucilloid in water prior to ingestion. The individual particles of the psyllium hydrophilic mucilloid tend to lump or agglomerate together when mixed with water. The psyllium hydrophilic mucilloid often fails to evenly disperse throughout the gelatinous mass and the hydration of psyllium hydrophilic mucilloid tends to take place over the exterior surface of such an agglomerated mass to form gelatin-coated lumps, the interiors of which are substantially dry. These gelatin-coated lumps are less voluminous than properly dispersed psyllium hydrophilic mucilloid and therefore the laxative benefits of the psyllium are compromised.
The poor dispersability of psyllium hydrophilic mucilloid is exacerbated by its poor mixing characteristics. Psyllium hydrophilic mucilloid is difficult to wet and tends to float on the surface of water. When mixing with water is attempted, the psyllium hydrophilic mucilloid forms lumps or masses. Psyllium is also difficult to mix when combined in the batter of a baked or continuously extruded food. Often, lumps of psyllium and material will result which result in an unacceptable food product due to textural deficiencies or to the poor taste of the psyllium material and psyllium derivatives.
In contrast to bulk-forming laxatives, osmotic laxatives act to retain water in the colonic lumen thereby counteracting the normal dehydrating action of the colon. By suppressing the dehydration action of the colon, the osmotic laxative produces a fecal stream which is softer, bulkier and easier to expel.
Lactitol may be used as an osmotic laxative because it is not absorbed in the small intestine and is thereafter hydrolysed and fermented in the large bowel by the action of intestinal microflora resulting in the liberation of galactose and sorbitol which are thereafter metabolized to organic acids and short chain fatty acids by colonic anaerobes. An osmotic effect is created in the colon, which normally acts to hydrate the fecal stream. The reduction in the dehydrating action of the colon produces a softer, bulkier fecal stream. Studies have shown that administration of 10 to 20 grams of lactitol daily results in a predictable laxation response of typically 24 hours or less. In contrast, other sugar alcohols have not proven to be effective osmotic laxatives and are therefore not recognized as such because they are unpredictable and not necessarily dose-dependent.
Additionally, lactitol exhibits other properties which makes it a preferred candidate for combination with psyllium. Specifically, lactitol does not induce an increase in blood glucose or insulin levels and contributes half the calories of most other carbohydrates (2 calories per gram). Because the control of blood glucose, lipids and body weight are primary goals in diabetes management, lactitol is considered to be a beneficial product for diabetics. Lactitol is also non-cariogenic and has a moderate, sugar-like sweetness. Lactitol also has good solubility, low hygroscopicity, and when provided in a crystalline form, is suitable for dry mixing. Finally, lactitol is also available at a price that is competitive with other sugar alcohols.
Thus, the two types of laxatives discussed above, bulk-forming and osmotic, operate by two entirely different mechanisms. Bulk-forming laxatives absorb water and expand in the colonic lumen; in contrast, osmotic laxatives retain water in the colonic lumen by osmosis.
While the prior art teaches the use of both types of laxatives and further teaches the use of psyllium as a bulk-forming laxative and the use of lactitol as an osmotic laxative, the prior art does not teach a combination of psyllium and lactitol. Further, the prior art does not teach the use of an osmotic laxative, such as lactitol, to enhance the compressibility, dispersability and mixability of bulk-forming laxatives, such as psyllium. One prior combination of psyllium and a sugar alcohol, specifically mannitol, is taught in U.S. Pat. No. 5,320,847 to Valentine et al. However, Valentine teaches the use of mannitol only as a low-calorie sweetener or substitute for free sugar, not as an osmotic laxative. Mannitol is not proven or recognized as a therapeutic osmotic laxative. Valentine also does not attempt to provide a psyllium laxative in a tablet form.
A laxative provided in tablet form could be designed either for immediate swallowing or chewing. As noted above, psyllium is not available in tablet form because it is simply not compressible. However, when combined with a sugar alcohol, such as lactitol, psyllium can be provided in a tablet form due to the sufficient compressibility of the psyllium/lactitol combination. The masticating action of the mouth aids in the dispersion of the psyllium. Providing psyllium in a tablet form also provides a vehicle whereby other ingredients, such as medications, minerals and vitamins can be delivered with the laxative material. Finally, tablets are easily transported by the consumer and easily dispensed by the pharmacist.
Two criteria are used to evaluate the quality of a tablet. Those two criteria are crushing strength or hardness and friability. Hardness is a measure of a tablet's strength. Hardness is measured by determining the lateral breaking strength expressed in kilograms, Strong Cobb Units (S.C.U.) or Newtons (N) exerted on a single tablet at the moment of rupture. Typical hardness testers are manufactured by Key Instruments. In the context of chewable tablets, the tablet hardness must be greater than about 30N to be commercially useful.
On the other hand, friability is another measure of a tablet's ability to resist chipping and breaking during shipment and handling. Friability is measured under standard conditions by weighing out a certain number of tablets (generally 20 or more) and placing them in a rotating plexiglass drum in which they are lifted during replicate revolutions by a radial louver and then dropped through the diameter of the drum. The tablets are then re-weighed and a percentage of the powder that has rubbed off is calculated. Friability of less than about 10% is considered to be acceptable for most chewable tablet contexts.
It is therefore an object of the present invention to provide an improved laxative by combining a bulk-forming laxative with an osmotic laxative.
Yet another object of the present invention is to provide an improved psyllium bulk-forming laxative by combining psyllium with an osmotic laxative.
Another object of the present invention is to provide an improved bulk-forming laxative/osmotic laxative combination which may be provided in tablet form or powder form.
It is still another object of the present invention to improve the compressibility, dispersability and mixability of psyllium husk powder by combining the psyllium husk powder with lactitol.
Yet another object of the present invention is to provide a means for producing a compressible psyllium/lactitol granulate using fluid bed granulation techniques.
Other objects and advantages of the invention will become apparent upon reading the summary, description of the preferred embodiments and the appended claims.
The above and other objects are accomplished by the present invention in which it has been discovered that a combination of lactitol as an osmotic laxative and psyllium as a bulk-forming laxative. The combination of the present invention results in an improved laxative with the qualities of both an osmotic laxative and an enhanced bulk-forming laxative due to the enhanced compressibility, dispersability and mixability of the psyllium.
One preferred embodiment involves the combination of psyllium hydrophilic mucilloid and lactitol. Specifically, approximately equal parts of psyllium hydrophilic mucilloid and lactitol are dry blended. The resulting powder mixture may be mixed with water and taken orally. Further, a binder solution may be subsequently mixed with the psyllium and lactitol to produce a granulate. The granulate may thereafter be dried and compressed into tablets.
If the granulate is to be compressed into tablets, the preferred form of lactitol is lactitol monohydrate. Three known binder solutions are available, including 60% lactitol solution, 3% polyvinylpyrrolidone (PVP) solution and 10% gelatin (250 Bloom) solution. The addition of 10% by weight microcrystalline cellulose has been found to improve the hardness and friability of the tablets.
If the resulting lactitol psyllium mixture is to be provided in a powder form, three known forms of lactitol are available. Specifically, the lactitol may be provided in the form of anhydrous lactitol crystals, lactitol monohydrate or anhydrous lactitol. It is preferred that the lactitol monohydrate and anhydrous lactitol monohydrate be milled to a maximum particle size of 125 microns or less. The preferred form of psyllium is Roeper (60 mesh).
The present invention may also be provided in the form of a baked product, such as a cookie, cracker or cake.